Three projects related to the treatment of intravenous drug abusers are included in this five year proposal; 1), pharmacotherapy for IV cocaine and opioid abuse, (inpatient (IP) n=100; outpatient (OP) n=440) 2. relapse prevention for pregnant cocaine abusers(n=60, 3. pharmacotherapy of HIV related cognitive impairment (IP n=50). These studies will occur within a 6 bed inpatient unit (1 month protocols) and 59 slot outpatient methadone and buprenorphine program (6 month protocols). Project 1 will examine dopamine agonists (amantadine, bromocriptine, mazindol) and antagonists (flupenthixol) and serotonergic augmentation of treatment (sertraline), as well as buprenorphine alone and in combination with these agents to treat cocaine abusing opioid addicts. Outpatient randomized clinical trials will use these medications within methadone or buprenorphine maintenance and include 6 month discontinuation studies (using 3 month placebo substitution at month 3 in half the group) to assess optimum duration of treatment. Neurobiological assessments including SPECT imaging of dopamine receptors, L-dopa and tryptophan challenges will be used to develop new medications for cocaine abuse treatment. Assessment of craving response to cocaine cue exposure will also provide information about treatment effects. Project 2 will use 3 weeks of intensive relapse prevention therapy to compare inpatient to 5 days per week outpatient treatment for 8 weeks will follow and outcome will be assessed at 6 months. Project 3 will compare pharmacotherapy with AZT, peptide T and/or cholinergic agents for HIV related cognitive impairment. Four week inpatient randomized clinical trials of detoxified opioid addicts and patients on methadone maintenance will be conducted. Outcome will focus on neuropsychological testing and SPECT blood flow scans. Overall, the Treatment Research Unit will provide innovative services to over 700 drug abusers at high risk for AIDS and its complications.